This project deals with the biological and molecular characterization of murine leukemia viruses (MuLV) with the goal of understanding host and viral factors involved in the pathogenesis of leukemias, lymphomas and a variety of non-neoplastic sequelae of infection with certain of these viruses. The primary subject of current study is the complex of viruses (LP-BM5 MuLV) responsible for induction of murine AIDS (MAIDS). Infection of sensitive strains of mice with this mixed virus stock, which contains a 4.9kb replication defective genome (BM5def) and B-tropic replication competent ecotropic and MCF helper MuLVs, results in progressive lymphoproliferative disease and immune system impairment, the disease process requiring BM5def and both B and CD4+ T cells. For studies of the precise role of BM5def in disease induction, cells have been transfected with the molecularly cloned genome, either native or modified by insertion of the marker gene for neomycin resistance (BM5def/neo(r). Analysis of virus rescued by use of replicating ecotropic or amphotropic helpers has shown that 1) the disease induced by helper-rescued BM5def is indistinguishable biologically and molecularly from MAIDS induced by LP-BM5 mixture; 2) MCF virus enhances efficiency of disease induction but is not required; 3) virus stocks rescued by cells cotransfected with neo(r) and BM5def or transfected with BM5def/neo(r) induce MAIDS but the cells and tissues from infected mice often contain BM5def-hybridizing fragments of sizes that reveal mutations in restriction endonuclease sites. In extending studies of whether MAIDS predisposes mice to secondary disease induced by normally innocuous agents, we have shown that 1) the severity of M-CMV-induced inclusion body disease is increased and extended in duration in adult mice infected for at least 6 wk with LP- BM5 MuLV; and 2) natural or experimental infection with C. freundii can result in hyperplastic to ulcerative colitis, often fatal. In studying the dysfunction of both CD4+and CD8+ T cells in mice with MAIDS it was shown that in infected mice impaired responses to mitogenic and antigenic stimuli were correlated with impaired calcium influx responses and the frequency of lymphocytes with prestimulation intracellular calcium was elevated.